The long range objective of this work is an understanding of how bacterial cells regulate their metabolic affairs so as to achieve an orderly yet flexible coordination of the several thousand chemical reactions necessary for growth. The immediate goals of the present work in Escherichia coli are: (a) to learn how the formation of aminoacyl-tRNA synthetases is regulated in bacteria; (b) to evaluate the operation of catabolite repression as a function of growth rate and to learn the metabolic basis for the transient nature of this control; (c) to elucidate the biochemical nature and biological significance of bacteriophage T4 conversion of valyl-tRNA synthetase; (d) to discover whether the formation of so-called constitutive enzymes is subject to some form of metabolic regulation; (e) to compare the participation in the repression of biosynthetic enzymes of endogenously generated endproduct and those derived from constituents of the medium; and (f) to examine the in vivo stability of a number of enzymes under a variety of growth conditions. The study will be conducted on a standardized bacterial cell system to permit the integration of biochemical, physiological and genetic data about a single cell. Use of conditionally-expressed lesions will permit control of cellular growth rate by any of a number of reactions in catabolism, anabolism and polymerization. Measurements of differential rates of accumulation of enzyme activities will be supplemented in key situations by measurement of in vivo inactivation or degradation of the enzyme by means of isotopic labeling. BIBLIOGRAPHIC REFERENCES: Neidhardt, F. C., Parker, J. and McKeever, W. G. 1975. Function and regulation of aminoacyl-tRNA synthetases in prokaryotic and eukaryotic cells. Annual Review of Microbiology. 29:215-250. Neidhardt, F. C. 1975. Regulation of aminoacyl-tRNA synthetases. In: Control of Ribosome Synthesis, edited by N. O. Kjeldgaard and O. Maaloe, Pp. 342-344.